| PART I. Resting-state fMRI study of burn patients withposttraumatic stress disorder using amplitude of low-frequencyfluctuation analysisBackgrounds and objective:Posttraumatic stress disorder (PTSD) is a widely acknowledged, long-standing clinicalproblems, and there is no particularly effective treatment, which mainly due to thepathogenesis of PTSD is unclear. As a severe trauma, burn can cause serious physical andpsychological effects on patients, and PTSD is one of the most prevalent mental disordersafter burn. Finding and understanding the pathophysiology of PTSD after burn haveespecially important significance for clinical treatment, physical and psychologicalrehabilitation of burn patients. The purpose of the current study is to explore the changes ofamplitude of low-frequency fluctuation (ALFF) of the resting state fMRI (rs-fMRI) in burnpatients with and without PTSD and to discuss its underlying neural mechanisms, andfurther to investigate the relationship between the intensity of abnormal spontaneousactivities and symptom severity of patients with PTSD.Methods：Totally16PTSD patients,16Non-PTSD patients who had been exposed to a severeburn and16healthy controls matched at gender, age and education level were examinedusing rs-fMRI, and ALFF were calculated to measure the spontaneous brain activity.Clinician administered posttraumatic stress disorder scale (CAPS) was used to assessed thesymptom severity of PTSD patients. The fMRI data were processed by SPM8, DPARSFand REST soft based on MATLAB2011b. Analysis of variance (ANOVA) was performed toexplore the discrepancies of spontaneous brain activities among the three groups, and posthoc t-tests was carried out to investigate the differences between groups respectively. Results were displayed using REST soft with a threshold of P<0.05corrected by AlphaSimmethods (combined height threshold of a P<0.05and a minimum cluster size of85voxels).Subsequently, the correlation between ALFF values of abnormal regions found in PTSDgroup and CAPS scores were analyzed.Results:1. No significant differences were found among the three groups in gender, age, andeducation level, and in durations post burn between the two burn patients groups (P>0.05).The CAPS scores were significantly different between the two burn patients groups(P<0.001).2. Compared with the healthy controls, increased ALFF was found in PTSD patients inthe left inferior frontal gyrus/middle frontal gyrus, right inferior frontal gyrus/insula andbilateral parahippocampal gyrus/anterior cingulate/medial frontal gyrus, while decreasedALFF was found in left lingual gyrus, and bilateral posterior cingulate/precuneus.3. Compared with the Non-PTSD patients, decreased ALFF was found in PTSDpatients in the right thalamus, while no increased ALFF was found in PTSD patients.4. Compared with the healthy controls, increased ALFF was found in Non-PTSDpatients in the right cerebellum, middle temporal gyrus, orbital frontal cortex, insula andleft parahippocampal gyrus, while no decreased ALFF was found in Non-PTSD patients.5. Pearson correlation analysis showed that ALFF values of the right thalamus inPTSD patients were significantly negatively correlated with CAPS scores (r=-0.63, P=0.008）.Conclusion:In conclusion, the present study observed abnormal spontaneous activities in burnpatients with and without PTSD, and verified the association between dysfunction ofprefrontal-limbic system and the pathophysiology of PTSD. The posterior cingulate cortexmay also play a role in the pathogenesis of PTSD. Moreover, the negative correlationbetween ALFF values of the right thalamus in PTSD patients and CAPS scores suggestedthat the thalamus may play an important role in the progression of PTSD, and spontaneousactivities of the thalamus can be used as an important basis to assess the symptom severityof PTSD. In addition, abnormal brain function of the burn patients may be also related tothe complicated response of stress after severe burn trauma. PART II. Abnormal functional connectivity in burn patients withposttraumatic stress disorder: A resting-state fMRI studyBackgrounds and objective:Although the neurocircuitry model of posttraumatic stress disorder (PTSD) has beenwidely recognized, but it remains limited for fully explaining the clinical symptoms ofPTSD. Recent researches have proposed that a broad range of neurological and psychiatricdisorders could be understood by evaluating dysfunction in three core neural networksincluding the default network (DMN), the central executive network (CEN), and thesalience network (SN), which may be related to the pathogenesis of PTSD. The aim of thisstudy is to explore whether there are aberrant functional connectivity or dysfunction of theneural networks in PTSD using resting state fMRI (rs-fMRI) functional connectivityanalysis, which based on the findings of partⅠand previous research, selecting the rightinsula, medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC) and rightthalamus as regions of interest (ROI) respectively, and further to investigate the clinicalsignificance of functional connectivity by focusing on their association with symptomseverity in PTSD patients.Methods：Totally16PTSD patients,16Non-PTSD patients who had been exposed to a severeburn and16healthy controls matched at gender, age and education level were examinedusing rs-fMRI, functional connectivity methods were used to analyze fMRI data. Clinicianadministered PTSD scale (CAPS) was used to assessed the symptom severity of PTSDpatients. The fMRI data were processed by SPM8, DPARSF and REST soft based onMATLAB2011b. ANOVA was performed to explore the differences of functionalconnectivity among the three groups for each ROI, results were displayed using REST softwith a threshold of P<0.05. Post hoc t-tests was carried out to investigate the differencesbetween groups respectively, and results were displayed using BrainNet Viewer with athreshold of P<0.05corrected by AlphaSim methods (combined height threshold of a P<0.005and a minimum cluster size of12voxels). Subsequently, the group differences offunctional connectivity in PTSD patients were correlated with the CAPS scores usingPearson correlation analysis.Results:1. No significant differences were found among the three groups in gender, age, andeducation level, and between the two burn patients groups in durations post burn (P>0.05).The CAPS scores were significantly different between the two burn patients groups(P<0.001).2. Compared with the healthy controls,(1) when the seed was located in the rightinsula, patients with PTSD showed decreased functional connectivity mainly in the bilateralcerebellum, left thalamus, left insula, left dorsal anterior cingulate cortex (dACC), rightinferior frontal gyrus, bilateral middle frontal gyrus, bilateral inferior parietal lobule, andright precuneus.(2) When the seed was located in MPFC, patients with PTSD showeddecreased functional connectivity mainly in the right insula and left precentral gyrus.(3)When the seed was located in PCC, patients with PTSD showed decreased functionalconnectivity mainly in the right medial frontal gyrus, and bilateral superior frontal gyrus, aswell as increased functional connectivity in the left cerebellum.(4) When the seed waslocated in the right thalamus, patients with PTSD showed decreased functional connectivitymainly in the left insula, and right precuneus, as well as increased functional connectivity inthe right cerebellum, and bilateral superior frontal gyrus.3. Compared with the Non-PTSD patients,(1) when the seed was located in the rightinsula, patients with PTSD showed decreased functional connectivity mainly in the leftcerebellum, left temporal pole, left thalamus, left superior temporal gyrus, right rostralanterior cingulate cortex (rACC), right orbital frontal cortex, and right inferior frontal gyrus.(2) When the seed was located in MPFC, patients with PTSD showed decreased functionalconnectivity mainly in the left cerebellum, as well as increased functional connectivity inthe right inferior parietal lobule, bilateral precuneus.(3) When the seed was located in PCC,patients with PTSD showed increased functional connectivity mainly in the left inferiortemporal gyrus, left lingual gyrus, right precuneus, bilateral inferior parietal lobule.(4)When the seed was located in the right thalamus, patients with PTSD showed decreasedfunctional connectivity mainly in the bilateral parahippocampal gyrus. 4. Compared with the healthy controls,(1) when the seed was located in the rightinsula, Non-PTSD patients showed increased functional connectivity mainly in the leftprecuneus.(2) When the seed was located in MPFC, Non-PTSD patients showed decreasedfunctional connectivity mainly in the right precuneus, left middle frontal gyrus, and leftposterior central gyrus.(3) When the seed was located in PCC, Non-PTSD patients showeddecreased functional connectivity mainly in the right medial frontal gyrus, and left middlefrontal gyrus.(4) When the seed was located in the right thalamus, Non-PTSD patientsshowed decreased functional connectivity mainly in the left dACC, and right precuneus, aswell as increased functional connectivity in the right cerebellum.5. Pearson correlation analysis showed that the strength of functional connectivitybetween the right insula and left dACC were negatively correlated with CAPS scores inPTSD patients.（r=-0.68, P=0.003）Conclusion:In conclusion, the present study observed abnormal functional connectivity mainly inthe DMN, CEN, SN, and cerebellum in burn patients with PTSD by analyzing rs-fMRI data.Our findings suggest that dysfunction of the three core neural network, and also abnormalfunctional connectivity in cerebellum may implicate the underlying pathophysiology inburn patients with PTSD. In addition, resting state functional connectivity within the SNmay be an imaging biomarker for assessment of the symptom severity of PTSD patients.Furthermore, dysfunction of the DMN in burn patients with and without PTSD may reflectthe disparate effects of PTSD and burn trauma exposure on brain function. |
PDF Full Text Request